Doxorubicin-Induced Oxidative Injury of Cardiomyocytes - Do We Have Right Strategies for Prevention?

Torres, Vukosava Milic; Dragojevic-Simic, Viktorija

doi:10.5772/34692

Cited by 6 publications

(3 citation statements)

References 162 publications

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“…DOX is one of the most widely used anthracycline drugs against leukemia and sarcoma. DOX is regarded as a very effective chemotherapeutic drug ( 78 ), due to its capacity to prevent the replication of cancer cells as a topoisomerase II inhibitor ( 140 , 141 ). As DOX forestalls topoisomerase II action, it forms a high oxidative and pro-inflammatory environment, thus causing DNA damage in cancer cells ( 140 , 142 ).…”

Section: The Role Of Taurine In Inflammationmentioning

confidence: 99%

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review)

Baliou

Kyriakopoulos²,

Spandidos

et al. 2020

Int J Oncol

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For one century, taurine is considered as an end product of sulfur metabolism. In this review, we discuss the beneficial effect of taurine, its haloamines and taurine upregulated gene 1 (TUG1) long non-coding RNA (lncRNA) in both cancer and inflammation. We outline how taurine or its haloamines (N-Bromotaurine or N-Chlorotaurine) can induce robust and efficient responses against inflammatory diseases, providing insight into their molecular mechanisms. We also provide information about the use of taurine as a therapeutic approach to cancer. Taurine can be combined with other chemotherapeutic drugs, not only mediating durable responses in various malignancies, but also circumventing the limitations met from chemotherapeutic drugs, thus improving the therapeutic outcome. Interestingly, the lncRNA TUG1 is regarded as a promising therapeutic approach, which can overcome acquired resistance of cancer cells to selected strategies. In this regard, we can translate basic knowledge about taurine and its TUG1 lncRNA into potential therapeutic options directed against specific oncogenic signaling targets, thereby bridging the gap between bench and bedside. Contents 1. The role of taurine in inflammation 2. Formation of taurine haloamines 3. Anti-microbial properties of taurine haloamines 4. Anti-inflammatory and anti-oxidant properties of taurine haloamines 5. Therapeutic perspectives and clinical studies 6. Significance of lncRNA TUG1 lncRNA in cancer 7. The association of lncRNA TUG1 and chemoresistance 8. The role of taurine or lncRNA TUG1 as a prognostic marker 9. Conclusions

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Section: The Role Of Taurine In Inflammationmentioning

confidence: 99%

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review)

Baliou

Kyriakopoulos²,

Spandidos

et al. 2020

Int J Oncol

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“…Dexrazoxane (DEX) is the sole FDA-approved medication for mitigating DOX-related cardiomyopathy [12]. DEX acts by binding to iron, reducing the pool of metal ions available for complex formation with anthracyclines, thereby reducing the generation of superoxide radicals and potentially limiting the production of reactive free radicals in the Fenton and Haber-Weiss reactions [13,14]. DOX disrupts the regular catalytic cycle of topoisomerase 2β (TOP2β), causing DNA strand breaks and potential cardiomyocyte death [10,15].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats

Szponar,

Gorska,

Ostrowska-Lesko

et al. 2024

IJMS

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Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study’s findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels.

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“…Other mechanisms include intracellular calcium dysregulation, impaired gene expression of various cardiac proteins [10], dysregulation of protein degradation by the ubiquitin-proteasome system [11], induction of mitochondrial DNA lesions [12], and targeting topoisomerase 2-beta [13] and mitochondrial topoisomerase [14]. The major metabolite of doxorubicin, doxorubicinol (doxo'ol) [15], is less potent than doxorubicin in its antitumour activity, although it may also contribute to the cardiotoxicity (reviewed in [16]).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic–pharmacodynamic modelling of acute N‐terminal pro B‐type natriuretic peptide after doxorubicin infusion in breast cancer

Liang

Brundage

Jacobson

et al. 2016

Brit J Clinical Pharma

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AIMSThe aim of the present study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to characterize the relationship between plasma doxorubicin and N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations within 48 h of doxorubicin treatment. METHODSThe study enrolled 17 female patients with stages 1-3 breast cancer and receiving adjuvant doxorubicin (60 mg m -2 ) and cyclophosphamide (600 mg m -2 ) every 14 days for four cycles. In two consecutive cycles, plasma concentrations of doxorubicin, doxorubicinol, troponin and NT-proBNP were collected before infusion, and up to 48 h after the end of doxorubicin infusion. Nonlinear mixed-effects modelling was used to describe the PK-PD relationship of doxorubicin and NT-proBNP. RESULTSA three-compartment parent drug with a one-compartment metabolite model best described the PK of doxorubicin and doxorubicinol. Troponin concentrations remained similar to baseline. An indirect PD model with transit compartments best described the relationship of doxorubicin exposure and acute NT-proBNP response. Estimated PD parameters were associated with large between-subject variability (total assay variability 38.8-73.9%). Patient clinical factors, including the use of enalapril, were not observed to be significantly associated with doxorubicin PK or NT-proBNP PD variability. CONCLUSIONThe relationship between doxorubicin concentration and the acute NT-proBNP response was successfully described with a population PK-PD model. This model will serve as a valuable framework for future studies to identify clinical factors associated with the acute response to doxorubicin. Future studies are warranted to examine the relationship between this acute response and subsequent heart failure. Should such a relationship be established, this model could provide useful information on patients' susceptibility to doxorubicin-induced long-term cardiotoxicity. British Journal of Clinical Pharmacology WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Doxorubicin is a first-line cytotoxic agent used for treating patients with malignancies, including breast cancer. However, total lifetime doses, and thus efficacy, are capped to limit the associated cardiomyopathy and congestive heart failure.• Despite limited total doses, cardiotoxicity can develop in 2-7% of patients months or even years after treatment, and angiotensin-converting enzyme (ACE) inhibitors are often prescribed to prevent and reduce severity.• Early predictive markers of susceptibility are needed, so patients at greatest risk could be identified and personalized approaches to treatment developed. WHAT THIS STUDY ADDS• N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin are commonly measured cardiac biomarkers, and we observed that plasma NT-proBNP concentrations dramatically increased 24-48 h after doxoburicin infusion, but troponin did not.• A population pharmacokinetic-pharmacodynamic model was developed to describe the relationship between doxorubicin exposure and the plasma acute NT-proBNP response.• High (...

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Doxorubicin-Induced Oxidative Injury of Cardiomyocytes - Do We Have Right Strategies for Prevention?

Cited by 6 publications

References 162 publications

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review)

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review)

Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats

Pharmacokinetic–pharmacodynamic modelling of acute N‐terminal pro B‐type natriuretic peptide after doxorubicin infusion in breast cancer

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